FI3556350T3 - Antiviraalisesti vaikuttavaa dihydrokinatsoliinijohdannaista, jolla on 4-asemassa S-konfiguraatio, sisältävä farmaseuttinen valmiste - Google Patents
Antiviraalisesti vaikuttavaa dihydrokinatsoliinijohdannaista, jolla on 4-asemassa S-konfiguraatio, sisältävä farmaseuttinen valmiste Download PDFInfo
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- FI3556350T3 FI3556350T3 FIEP19176985.0T FI19176985T FI3556350T3 FI 3556350 T3 FI3556350 T3 FI 3556350T3 FI 19176985 T FI19176985 T FI 19176985T FI 3556350 T3 FI3556350 T3 FI 3556350T3
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- Prior art keywords
- solution
- methoxy
- acid
- fluoro
- methoxyphenyl
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- 239000000825 pharmaceutical preparation Substances 0.000 title claims 91
- 230000000840 anti-viral effect Effects 0.000 title claims 5
- NTURVSFTOYPGON-UHFFFAOYSA-N Dihydroquinazoline Chemical class C1=CC=C2C=NCNC2=C1 NTURVSFTOYPGON-UHFFFAOYSA-N 0.000 title claims 2
- 239000000243 solution Substances 0.000 claims 147
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 61
- 239000002253 acid Substances 0.000 claims 49
- 150000003839 salts Chemical class 0.000 claims 46
- 150000001875 compounds Chemical class 0.000 claims 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 40
- 238000000034 method Methods 0.000 claims 38
- 238000002360 preparation method Methods 0.000 claims 37
- 239000012453 solvate Substances 0.000 claims 36
- 239000011550 stock solution Substances 0.000 claims 36
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 34
- 239000000203 mixture Substances 0.000 claims 31
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims 30
- 229920000858 Cyclodextrin Polymers 0.000 claims 26
- 239000008215 water for injection Substances 0.000 claims 26
- 238000004519 manufacturing process Methods 0.000 claims 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 23
- 239000007787 solid Substances 0.000 claims 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 21
- 239000002904 solvent Substances 0.000 claims 19
- 241000701024 Human betaherpesvirus 5 Species 0.000 claims 18
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 18
- 239000002585 base Substances 0.000 claims 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 16
- 229940097362 cyclodextrins Drugs 0.000 claims 16
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- FWYSMLBETOMXAG-UHFFFAOYSA-N 2-[8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4h-quinazolin-4-yl]acetic acid Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N(C(CC(O)=O)C3=CC=CC(F)=C3N=2)C=2C(=CC=C(C=2)C(F)(F)F)OC)=C1 FWYSMLBETOMXAG-UHFFFAOYSA-N 0.000 claims 12
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 12
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- 238000011282 treatment Methods 0.000 claims 11
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 9
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- 229910052763 palladium Inorganic materials 0.000 claims 9
- 230000009385 viral infection Effects 0.000 claims 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 8
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- 241000700586 Herpesviridae Species 0.000 claims 8
- 239000003480 eluent Substances 0.000 claims 8
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- 239000012442 inert solvent Substances 0.000 claims 8
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- 239000000126 substance Substances 0.000 claims 8
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 7
- 239000000470 constituent Substances 0.000 claims 7
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- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims 6
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 6
- 238000005481 NMR spectroscopy Methods 0.000 claims 6
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- -1 alkali metal salts Chemical class 0.000 claims 6
- 230000015572 biosynthetic process Effects 0.000 claims 6
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 5
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- 239000006143 cell culture medium Substances 0.000 claims 5
- 238000010586 diagram Methods 0.000 claims 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims 5
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- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 claims 4
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- 235000014852 L-arginine Nutrition 0.000 claims 4
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- 235000019799 monosodium phosphate Nutrition 0.000 claims 4
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- 230000002265 prevention Effects 0.000 claims 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims 4
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 claims 4
- 238000003756 stirring Methods 0.000 claims 4
- 238000000825 ultraviolet detection Methods 0.000 claims 4
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims 3
- 241000701022 Cytomegalovirus Species 0.000 claims 3
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- NJWCVQBHNBLNOZ-ZRMYETLXSA-N (1S,3R,5R,6S,8R,10R,11S,13S,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,47R,48S,49R)-5,20,30,35-tetrakis(hydroxymethyl)-49-(2-hydroxypropoxy)-10,15,25-tris(2-hydroxypropoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,47,48-dodecol Chemical compound CC(O)COC[C@H]1O[C@@H]2O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@@H]6[C@@H](COCC(C)O)O[C@H](O[C@@H]7[C@@H](CO)O[C@H](O[C@@H]8[C@@H](COCC(C)O)O[C@H](O[C@H]1C[C@H]2O)[C@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O)[C@H](OCC(C)O)[C@H]3O NJWCVQBHNBLNOZ-ZRMYETLXSA-N 0.000 claims 2
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- 230000006641 stabilisation Effects 0.000 claims 1
- 238000011105 stabilization Methods 0.000 claims 1
- 150000008163 sugars Chemical class 0.000 claims 1
- 150000003460 sulfonic acids Chemical class 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 241001529453 unidentified herpesvirus Species 0.000 claims 1
- 238000001291 vacuum drying Methods 0.000 claims 1
- 229940093257 valacyclovir Drugs 0.000 claims 1
- 229960002149 valganciclovir Drugs 0.000 claims 1
- 229910052727 yttrium Inorganic materials 0.000 claims 1
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Claims (20)
1. Laskimonsisäisesti annettavaksi tarkoitettu farmaseuttinen val- miste, joka sisältää seuraavia ainesosia nimittäin a) ({8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2-metoksi-5- —(trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yylijetikkahappoa, jossa dihyd- rokinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S-konfiguraatio, tai sen suolaa, solvaattia tai suolan solvaattia, b) syklodekstriineistä valittua apuainetta, ja Cc) vettä.
2. Patenttivaatimuksen 1 mukainen farmaseuttinen valmiste, joka si- sältää lisäksi ainakin yhtä puskurointiainetta, joka on valittu fosfaattipuskureista, Tris-puskureista ja sitraattipuskureista.
3. Patenttivaatimuksen 1 tai 2 mukainen farmaseuttinen valmiste, joka sisältää lisäksi ainakin yhtä sokeria.
4. Patenttivaatimuksen 3 mukainen farmaseuttinen valmiste, jossa sokeri on valittu ryhmästä, joka koostuu glukoosista, sakkaroosista, laktoosista, maltoosista, trehaloosista, sorbitolista ja mannitolista.
5. Minkä tahansa patenttivaatimuksen 1-4 mukainen farmaseuttinen valmiste, tunnettu siitä, että se sisältää {8-fluori-2-[4-(3-metoksifenyyli)pi- peratsin-1-yyli]-3-[2-metoksi-5-(trifluorimetyyli)fenyylil-3,4-dihydrokinatsolin-4- yylijetikkahappoa, jossa dihydrokinatsolirenkaan 4-asemassa sijaitsevalla hii- lellä on S-konfiguraatio, tai sen suolaa, solvaattia tai suolan solvaattia määrän, joka vastaa 1-100 mg:aa puhdasta vaikuttavaa ainetta millilitraa kohden valmis- tetta.
6. Minkä tahansa patenttivaatimuksen 1-5 mukainen farmaseuttinen valmiste, tunnettu siitä, että valmisteen pH on 7,5—8,5.
7. Minkä tahansa patenttivaatimuksen 1-6 mukainen farmaseuttinen valmiste, tunnettu siitä, että kyseistä ainakin yhtä apuainetta on läsnä 1-5 ekvivalenttia suhteessa (8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2- metoksi-5-(trifluorimetyyli)fenyylil-3,4-dihydrokinatsolin-4-yyli}etikkahappo-si- sältöön.
8. Minkä tahansa patenttivaatimuksen 1-7 mukainen farmaseuttinen formulaatio, tunnettu siitä, että kyseistä ainakin yhtä apuainetta on läsnä 2-5 ekvivalenttia suhteessa {8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3- [2-metoksi-5-(trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yyli}etikka-happo- sisältöön.
9. Minkä tahansa patenttivaatimuksen 1-6 mukainen farmaseuttinen valmiste, tunnettu siitä, että apuaine on valittu B-syklodekstriineistä ja muunnetuista B-syklodekstriineistä, erityisesti hydroksialkyyli-B-syklodekstrii- neistä, alkyylihydroksialkyyli-B-syklodekstriineistä ja sulfoalkyylieetteri-B-syklo- dekstriineistä.
10. Patenttivaatimuksen 9 mukainen farmaseuttinen valmiste, tun - nettu siitä, että valmiste sisältää suhteessa sen {8-fluori-2-[4-(3-metoksi- fenyyli)piperatsin-1-yyli]-3-[2-metoksi-5-(trifluorimetyyli)fenyyli]-3,4-dihydroki- natsolin-4-yylijetikkahapposisältöön 1—10 ekvivalenttia syklodekstriiniä ja 0—2,0 ekvivalenttia NaOH:a.
11. Minkä tahansa patenttivaatimuksen 1-6 tai patenttivaatimuksen 9 tai 10 mukainen farmaseuttinen valmiste, tunnettu siitä, että se sisältää sataa millilitraa kohden a) 0,5 - 2,5 g {8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2- metoksi-5-(trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yylijetikkahappoa, jossa dihydrokinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S-konfiguraa- tio, tai sen suolaa, solvaattia tai suolan solvaattia, b) 10,0 - 30,0 g HP-B-syklodekstriiniä, c) 0,0 - 350 mg, erityisesti 100 - 125 mg, NaOH:a ja d) vettä, missä valmisteen pH on 7,5 - 8,5.
12. Minkä tahansa patenttivaatimuksen 1-6 tai patenttivaatimuksen 9—11 mukainen farmaseuttinen valmiste, tunnettu siitä, että se sisältää sa- taa millilittaa kohden a) edullisesti 1,0 - 2,0 g {8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1- yyli]-3-[2-metoksi-5-(trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yylijetikka- happoa, jossa dihydrokinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S- konfiguraatio, tai sen suolaa, solvaattia tai suolan solvaattia, b) edullisesti 12,5 - 22,5 g HP-B-syklodekstriiniä, c) edullisesti 75 - 225 mg, erityisesti 100 - 125 mg, NaOH:a ja d) vettä, missä valmisteen pH on 7,5 - 8,5.
13. Kiinteä farmaseuttinen valmiste, joka on valmistettu kylmäkuivaa- malla minkä tahansa patenttivaatimuksen 1-12 mukainen farmaseuttinen val- miste.
14. Menetelmä minkä tahansa patenttivaatimuksen 1-8 mukaisen farmaseuttisen valmisteen valmistamiseksi, joka menetelmä käsittää seuraavat vaiheet nimittäin A) kyseisen ainakin yhden apuaineen liuottamisen veteen, B) {8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2-metoksi-5- (trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yyli}etikkahapon, jossa dihydro- kinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S-konfiguraatio, tai sen suo- lan, solvaatin tai suolan solvaatin lisäämisen vaiheessa A) saatuun liuokseen, C) mahdollisesti kyseisen ainakin yhden sokerin ja/tai ainakin yhden puskurointiaineen lisäämisen, D) pH:n säätämisen haluttuun arvoon farmaseuttisen valmisteen ai- kaansaamiseksi, ja E) vaiheessa D) saadun liuoksen sterilointisuodatuksen ja pakkaami- sen sopiviin säiliöihin, F) mahdollisesti vaiheessa E) saadun liuoksen loppusteriloinnin kuu- mentamalla.
15. Menetelmä minkä tahansa patenttivaatimuksen 1-8 mukaisen farmaseuttisen valmisteen valmistamiseksi, joka menetelmä käsittää seuraavat vaiheet nimittäin
I.) kyseisen ainakin yhden apuaineen liuottamisen osaan vedestä,
II.) {8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2-metoksi-5- (trifluorimetyyli)fenyyli]-3,4-dihydrokinatsolin-4-yyli}etikkahapon, jossa dihydro- kinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S-konfiguraatio, tai sen suo- lan, solvaatin tai suolan solvaatin lisäämisen vaiheessa |.) saatuun liuokseen,
III.) mahdollisesti vaiheessa II.) saadun liuoksen pH:n säätämisen ha- luttuun arvoon ensimmäisen liuoksen aikaansaamiseksi,
IV.) ainakin yhden sokerin ja/tai ainakin yhden puskurointiaineen liu- ottamisen osaan vedestä,
V.) mahdollisesti vaiheessa IV.) saadun liuoksen pH:n säätämisen haluttuun arvoon toisen liuoksen aikaansaamiseksi,
VI.) ensimmäisen ja toisen liuoksen sekoittamisen keskenään farma- seuttisen valmisteen aikaansaamiseksi, ja
VII.) vaiheessa VI.) saadun liuoksen sterilointisuodatuksen ja pak- kaamisen sopiviin säiliöihin, VIII.) mahdollisesti vaiheessa VII.) saadun liuoksen loppusteriloinnin kuumentamalla.
16. Menetelmä minkä tahansa patenttivaatimuksen 1-6 tai 9-12 mu- kaisen farmaseuttisen valmisteen valmistamiseksi, joka menetelmä käsittää seuraavat vaiheet nimittäin a.) (8-fluori-2-[4-(3-metoksifenyyli)piperatsin-1-yyli]-3-[2-metoksi-5- (trifluorimetyyli)fenyylil-3,4-dihydrokinatsolin-4-yyli}etikkahapon, jossa dihydro- kinatsolirenkaan 4-asemassa sijaitsevalla hiilellä on S-konfiguraatio, tai sen suo- lan, solvaatin tai suolan solvaatin lisäämisen NaOH:n vesiliuokseen, edullisesti NaOH:n 0,1 M vesiliuokseen, liuoksen tai suspension valmistamiseksi,
b.) veden lisäämisen vaiheessa a.) saatuun liuokseen tai suspensi- oon,
c.) syklodekstriinin ja NaCI:n lisäämisen vaiheessa b) saatuun liuok- seen tai suspensioon,
d.) vaiheessa c.) saadun liuoksen sterilointisuodatuksen ja pakkaa- misen sopiviin säiliöihin,
e.) mahdollisesti vaiheessa d.) saadun liuoksen loppusteriloinnin kuu- mentamalla.
17. Menetelmä patenttivaatimuksen 13 mukaisen kiinteän farmaseut- tisen valmisteen valmistamiseksi, joka menetelmä käsittää farmaseuttisen val- misteen valmistamisen minkä tahansa patenttivaatimuksen 14-16 mukaisella menetelmällä, mitä seuraa vaihe, jossa saatu farmaseuttinen valmiste kylmä- kuivataan kiinteän farmaseuttisen valmisteen aikaansaamiseksi.
18. Minkä tahansa patenttivaatimuksen 1-13 mukainen farmaseutti- nen valmiste tarkoitettuna käytettäväksi menetelmässä sairauksien hoitamiseksi ja/tai ennalta ehkäisemiseksi.
19. Minkä tahansa patenttivaatimuksen 1-13 mukainen farmaseutti- nen valmiste tarkoitettuna käytettäväksi virusinfektioiden hoitoon ja/tai ennalta- ehkäisyyn.
20. Minkä tahansa patenttivaatimuksen 1-13 mukainen farmaseutti- nen valmiste tarkoitettuna käytettäväksi HCMV:n tai muiden herpesvirusten ryh- män edustajien aiheuttamien infektioiden hoitoon.
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| DE102012101680A DE102012101680A1 (de) | 2012-02-29 | 2012-02-29 | Pharmazeutische Zubereitung enthaltend ein antiviral wirksames Dihydrochinazolinderivat |
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| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| JP6445546B2 (ja) * | 2013-06-19 | 2018-12-26 | アイキュリス アンチ−インフェクティブ キュアズ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 非晶質レテルモビル及び経口投与のためのその固形医薬製剤 |
| EP3463064B1 (en) | 2016-06-03 | 2021-11-03 | Atreya Innovations Private Limited | A device for the detection and reliable capturing of the pulse characteristics |
| MY196966A (en) * | 2017-03-06 | 2023-05-15 | Everest Medicines Singapore Pte Ltd | Solid forms and combination compositions comprising a beta-lactamase inhibitor and uses thereof |
| UY39095A (es) * | 2020-02-27 | 2021-09-30 | Aic246 Gmbh & Co Kg | Composiciones farmacéuticas que comprenden acetato de 2- [(4s)-8-fluoro-2-[4-(3-metoxifenil)piperazin-1-il]-3-[2-metoxi-5- (trifluorometil)fenil]-4h-quinazolin-4-il] e iones de sodio |
| UY39099A (es) | 2020-02-27 | 2021-08-31 | Aic246 Gmbh & Co Kg | 2-[(4s)-8-fluoro-2-[4-(3-metoxifenil)piperazin-1-il]-3-[2-metoxi-5-(trifluorometil)fenil]-4h-quinazolin-4-il] acetato de sodio y composiciones farmacéuticas del mismo |
| CN114539085B (zh) * | 2020-11-26 | 2023-10-20 | 山东诚创蓝海医药科技有限公司 | 一种脲基衍生物的制备 |
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| CN115322157B (zh) * | 2022-06-02 | 2023-12-05 | 浙江车头制药股份有限公司 | 来特莫韦中间体化合物及其制备方法和应用 |
| CN115677539B (zh) * | 2022-11-01 | 2023-10-24 | 南京工业大学 | 一种温和条件下钴催化脲基导向芳烃的高选择性单烯基化的方法 |
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| CA1242699A (en) * | 1985-02-01 | 1988-10-04 | Bristol-Myers Company | Cefbuperazone and derivatives thereof |
| FR2585705B1 (fr) * | 1985-08-05 | 1989-01-13 | Bristol Myers Co | Sels de cephalosporine et compositions injectables |
| JP3552240B2 (ja) * | 1993-02-23 | 2004-08-11 | 第一製薬株式会社 | 高濃度ｔｃｆ製剤 |
| JPH11209277A (ja) * | 1998-01-19 | 1999-08-03 | Yoshitomi Pharmaceut Ind Ltd | 医薬組成物 |
| IT1304190B1 (it) * | 1998-12-18 | 2001-03-08 | Euphar Group Srl | Clatrati di deidroepiandrosterone e relative composizionifarmaceutiche |
| IL145357A0 (en) * | 1999-03-17 | 2002-06-30 | Astrazeneca Ab | Amide derivatives |
| AU2000249111A1 (en) * | 2000-05-30 | 2001-12-11 | Dr. Reddy's Research Foundation | New pharmaceutical composition and the process for its preparation |
| DE10319612A1 (de) * | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| CA2546932A1 (en) * | 2003-11-25 | 2005-06-09 | Chiron Corporation | Quinazolinone compounds as anticancer agents |
| ATE421518T1 (de) | 2005-02-10 | 2009-02-15 | Bristol Myers Squibb Co | Dihydrochinazolinone als 5ht-modulatoren |
| DE102005027517A1 (de) | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| US8743287B2 (en) * | 2009-07-24 | 2014-06-03 | Broadcom Corporation | Method and system for mitigating motion trail artifacts and improving low contrast contours in temporal filtering based noise reduction |
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